Genes encoding mitochondrial respiratory chain components are profoundly down-regulated with aging in the cochlea of DBA/2J mice
Genes encoding mitochondrial respiratory chain components are profoundly down-regulated with aging in the cochlea of DBA/2J mice
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DOI：
10.1016/j.brainres.2007.08.090
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发表时间：
2007-11-28
期刊：
影响因子：
2.9
通讯作者：
Tanokura, Masaru
中科院分区：
文献类型：
--
作者：
Someya, Shinichi;Yamasoba, Tatsuya;Tanokura, Masaru
听觉相关性听力损失（阿勒）是随着年龄增长而逐渐丧失的听觉功能。DBA/2 J小鼠的Cdh 23基因突变导致3月龄的阿勒。听性脑干反应（ABR）检测结果证实，8月龄小鼠听力损失严重，2月龄小鼠听力损失轻微。使用Affyssin微阵列测量2月龄和8月龄DBA/2 J小鼠的cobiar基因表达。全面的基因表达分析在超过4000个耳蜗基因中发现了与阿勒相关的显着表达变化。8月龄DBA/2 J小鼠耳蜗中AHL相关基因与15种线粒体过程类别统计学相关，包括“线粒体电子传递链”、“氧化磷酸化”、“呼吸链复合体I”、“呼吸链复合体IV”和“呼吸链复合体W”。此外，编码线粒体呼吸链复合体I，II，III，IV和V的31个基因在耳蜗中显著下调。定量RT-PCR（QRT-PCR）验证了选定的一组基因的微阵列数据。因此，这些观察结果提供了证据表明，阿勒与老年DBA/2 J小鼠耳蜗中线粒体呼吸链复合体相关基因的显著下调有关。(C)2007 Elsevier B. V.保留所有权利。
Age-related hearing loss (AHL) is the progressive loss of auditory function with aging. Mutations in the Cdh23 gene of DBA/2J mice result in AHL by 3 months of age. Hearing function was analyzed by auditory brainstem response (ABR) which confirmed that severe age-related hearing loss occurred in 8-month-old mice, whereas mild hearingloss occurred in 2-month-old mice. Cochlear gene expression of 2-month-old and 8-month-old DBA/2J mice was measured using Affymetrix microarrays. Comprehensive gene expression analysis identified significant expression changes correlated with AHL in over 4000 cochlear genes. AHL-correlated genes in the cochlea of 8-month-old DBA/2J mice were statistically associated with 15 mitochondrial process categories, including "mitochondrial electron transport chain", "oxidative phosphorylation", "respiratory chain complex I", "respiratory chain complex IV", and "respiratory chain complex W. Furthermore, 31 genes encoding components of the mitochondrial respiratory chain complexes I, II, III, IV, and V were significantly downregulated in the cochlea. Quantitative RT-PCR (QRT-PCR) validated the microarray data in a selected set of genes. Thus, these observations provide evidence that AHL is associated with profound down-regulation of genes involved in the mitochondrial respiratory chain complexes in the cochlea of aged DBA/2J mice. (C) 2007 Elsevier B.V. All rights reserved.